Gastrointestinal pathology Flashcards Preview

– Acid damage to stomach mucosa. 

– Due to imbalances between mucosal defences and acidic enviromnet. Defence include (mucin produced by the foveolar cell, bicarbonate secretion by surface epithelium and normal blood supply) 

– Severe burn (ulcer due to severe burn are called curling ulcers)→hypovolemia→reduced blood supply to the stomach→reduced transsport of nutrients to mucosa and removal of the acid 

–NSAIDs →decreases prostaglandin. (Prostaglandin decreases acid production, stimulates cells to secrete bicarbonate and mucus and also increass blood flow in the stomach)

– Heavy alcohol consumption

– chemotherapy

– Increased intracranial pressure (cushin ulcer if causes acute gastritis)→ increased vagal stimulation→increased production of acetylcholine→Increased acid production by stomach (note: acetylcholine, histamine and gastrin increases acid production in stomach) 

– Shock leads to decreased blood flow to the stomach, and In ICU patient in shock can get multiple ulcer (stress ulcers).

– Superficial inflammation 

– Erosion (loss of epithelium)

– Ulcer (loss of mucosal layer)

– Chronic inflammation of stomach mucosa

– There are two type: chronic Autoimmune gastritis and Chronic H pylori gastritis 

– Chronic autoimmune gastritis: Autoimmune destruction of gastric parietal cells (located predominantly in fundus and body of the stomach)

• Parietal cells are destroyed by the T-cell mediated reaction (type IV Hypersensitivity)

• As a consequence of the damage antibodies are produced against parietal cell or intrinsic factor. Antibodies are used for diagnosis

– Atrophy of the mucosa (loss of parietal cells) with intestinal metaplasia

– Achlorhydria (low acid production by the stomach)  with increased gastrin level and antral G-hyperplasia: loss of parietal cell→decreased acid in the stomach→increased gastrin levels to increase acid production→antral G-cell hyperplasia

– Megaloblastic (pernicious) anemia due to lack of intrinsic factor (instrinsic factors are produced by parietal cells and is involved in obsorption of vit-B12)

– Increased risk for gastric adenocarcinoma (intestinal type)

– Is the most common form of gastritis caused by the H pylori induced acute and chronic inflammation. 

– H pylori produces proteases and ureases→inflammatin of the stomach mucosa and consequently weakening mucosal defenses. Antrum is the most common site of     H pylori gastritis.

Presentation:

– Epigastric abdominal pain

– Increased risk for ulceration, gastric adenocarcinoma (chronic inflmmation→intestinal metaplasia→adenocarcinoma), MALT (mucosa associated lymphoid tissue) Lymphoma

Treatment: involves the triple therapy

– Resolves gastritis→ulcers is resolved, intestinal metaplasia is reversed and the risk for lymphoma will also disappears.

– Negative urea breath test indicate the H pylori bacteria is killed

– lack of stool antigen confirm killing of H pylori.

– Solitary mucosal ulcers involving proximal duodenum (90%) and in distal stomach (10 %).

– Duodenal ulcer is almost always due to H pylori (90%) and rarely it is due to ZE (Zollinger-Ellison) syndrome.

– Presents with epigastric that improves with meal: during meal neutralizing substances is formed 

– Endoscopic biopsy show ulcers with hyptertrophy of  brunner glands

– Complication of duodunal ulcers is that it may rupture and lead to bleeding from the gastroduodenal arter (anterior ulcers) or acute pancreatitis (posterior ulcers)

– It is the second type of peptic ulcer disease

– Usually caused by H pylori and other cause include NSAIDs and bile reflux.

– Presents with epigastric pain that worsens during meals due to increased acid prodcution

– commonly found in the antrum of the lesser curvature and rupture of the ulcers causes bleeding from the left gastric artery. 

–

– differential diagnosis of ulcer includes cancer

– Duodenal ulcers are almost never malignant. It is very rare 

– Gastric ulcers can be caused by gastric carinoma

– Benigh peptic ulcer: usuall small (< 3 cm), sharply demarcated (punched out) and surrounded by radiating fold of mucosa

– Malignant ulcer: large and irregular with heaped up margins

– biopsy of ulcer is required for definite diagnosis

– Malignant proliferation of surface epithelium (simple columnar epithelium) of stomach: It is adenocarcinoma

– subclassified into two types: intestinal type and diffuse type

– Intestinal type: more common, presents as large irregular ulcer with heaped up margins and most commonly involves the antrum of the lesser curvature.

• Risk factors: intestinal metaplasia ( due to H pyloru and autoimmune gastritis), Nitrosamine in smoked food (japan) and blood type A.

– Diffuse type: characterized by signet ring cells (cell with nucleus pushed to the side by mucin) diffusely infiltrating gastric wall→desmoplasia (growth of fibrous or connective tissue as a response to neoplasm)

•Desmoplasia leads to thickening of stomach wall (linitis plastica)

•Not associated with H pylori, intestinal metaplasia or nitrosamine

– Presents late and include weight loss, abdominal pain, anemia, and early satiety

– Rarely presents with acanthosis nigricans (darkening and thickening of the skin) and Leser Trelat sign (Multiple seborrheic keratoses)

– Spreads to left supraclavicular lymph node (virchow node) which is one of the lymph node that drains the stomach

– Distant metastasis commonly involve the liver 

– Other sites of metastasis: preumbilical region (Sister Mary Joseph Nodule) seen with intestinal type, and Bilateral ovaries (Krukenburg Tumor) seen with diffuse type.

– Congenital defect of duodenum to canalize

– Highlig associated with Downsyndrome

Clinical features:

– Polyhydramnios: baby swallows the amniotic fluid but fluid can not enter the intestine for absorption

– Bilious vomiting

– Distension of stomach and distension of duodenum→double-bouble sign.

– Congenital outpouching of all three layers of small intestine, caused by persistance of viteline duct (Formed between midgut and yolk sac during the 4th gestation week. Function is transport nutrients to midgut. Dissapear by 7th gestation week)

– Persistance of viteline duct after 7th week→ Meckel diverticulum

– True diverticulum: involves muscosa, submucosa and muscularis mucosa

– Rule of 2s:

• Seen in 2% of population (most common congenital defect of GIT)

• 2 inches long and 2 feet from ileocecal valve

•Presents during the first 2 year of life 

Clinical feature:

– Bleeding due to heterotopic gastric mucosa 

– Volvulus

– Intussusception

– Obstruction

–

– Is twisting of bowel along its mesentery 

– Can cause obstruction of bowel, cutting off blood supply to the affected area→infarction

– Most common location: sigmoid colon (Elderly) and Cecum (young adults)

–Telescoping of the proximal segment of the bowel forward into distal segment.

– telescoped segment is pulled forward by persitalsis→obstruction of the bowel and disruption of the blood supply

– Blood supply to the affected area is reduced→infarction

– In adults common cause is tumor and in children it is lyphoid hyperplasia (commonly arises in the terminal ileum) 

– Most causes are idiopathic 

Risk factors:

–having had previously one

– having a sibling with intussusception

– Having intestinal malrotation

Symptoms

–First sign is intermittent abdominal pain which gets worse with persitalsis

– Vomiting 

– Presence of hard, sausage-like mass in the abdomen.

– Red currant jelly stool (Due to sloughing off of intestinal mucusa, blood and mucus)

– Sepsis and Fever: Rupture of the bowel (because of infarction)→ release of bacteria 

Diagnosis:

–Children: Intussusception can often be felt during rectal examination 

– Definite diagonsis require CT, x-ray or ultrasound: displays the inussuscept segment.

Treatment:

– Barrium or air enema can be used to unfold the intussusception 

– Surgery can also be required 

– Small bowel is highly succeptible to ischemic injury because of high demand for oxygen and nutrients

– Ischemic injury→ transmural infarction with imbolism/thrombosis of the superior mesenteric artery or thrombosis of the superior mesenteric vein.

–Muscosal infarction occurs with marked hypotension: Hypotension reduces blood supply distally to the mucosa leading to infarction.

clinical features:

– Abdominal pain, bloody diarrhea and decreased bowel sounds. 

Treatment:

– Give enough fluid

– Manage pain

– Antibiotics 

– Definitive treatment includes reestablishing blood to the small bowel, use of thrombolytic enzymes and surgical resection of the infarcted tissue.

– Decreased function of the lactase enzyme, which is found in the brush border of the enterocytes.

• Lactase normally breaks down lactose into glucose and galactose, and enterocytes absorbs both glucose and galactose. In lactose intolerance lactose is not broken down in the small bowel.

– Presents with abdominal diarrhea and distension upon consumption of milk products. Because lactose is osmotically active

– Deficiency of the lactase enzyme can be congenital (rare autosomal recessive disorder: enzyme is missing) or acquired (aging→downregulation of lactase enzyme gene, infection damages the microvilli→temporary deficiency until microvilli heals)

–Immune mediated damage to the small bowel villi due to exposure to gluten: associated with HLA-DQ2 or DQ8.

• Gluten is broken down in thet stomach and the pathogenic component in Gluten responsible for Celiac disease is Gliaden. 

• Gliaden binds to IgA on mucosal surface of the epithelial cells in small intestine. IgA-gliaden complex is usually destroyed by immunes system, but not in celiac disease

• The complex binds to transferrin receptors and is transported to the lamina propria.

• In lamina propria the enzyme tissue transglutaminase (tTG) removes an amide group from gliaden.

• The deamidated gliaden is engulfed by macrophages and presented by MHC-II (HLA-DQ2 or DQ8)

• T-helper CD4⁺ binds to MHC-II release inflammatory cytokine, stimulates B-cell to secrete IgA mediated anti-gliaden, anti-tTG and anti-endomysial (antibodies against tTG in endomysium) and recruit  CD8⁺ killer cells.

• Inflammatory cytokines and CD8⁺ killer cell damages the epithelial cells

Clinical presentation:

–Affects the whole small intestine, but most commonly the duodenum.

– Children: abdominal distension, diarrhea and bloating

– Adult: Chronic diarrhea and bloating

– Dematitis herpetiformis: IgA antibodies bind to epidermal transglutaminase→inflammatory reaction→formation of vesicles in dermal papillae (blisters)

Laboratory finding:

– IgA mediated anti-tTG, anti-gliaden and antibodies against endomysium.

–IgG is also present and used in patient with IgA deficienty

– Flattened villie, hyperplastic crypts and intraepithelial lymphocytes infiltration. 

– Small bowel carcinoma and T-cell lymphoma are late complications (EATL: Enteropathy Associated T-cell Lymphoma)

–

– Gastrointestinal disease where damage to small villie due to an unkown organism results in malabsorption

– The villie are flattened→less nutrient is absorbed→Malabsorption of Vit-B12 and Folate.  

– Unlike Celiac disease tropical sprue

• Occurs in tropical regions (e.g. Carribean

• Arises after infectious diarrhea and responds to antibiotics

• Most damage occurs in jejunum and ileum (Vit-B12 and folate deficiency) and duodenum is less commonly involved.

Symptoms:

– Related to intestinal injury and malabsorption

– Diarrhea, abdominal pain, fatigue, weight loss and dehydration

– Complication from malabsorption is megaloblastic anemia   

Diagnosis:

– Patient has lived in tropics and have chronic GIT symptoms and malabsoprtion.

– Fat malabsorption: 72 hour stool collection on prescribed diet. 

– Carbohydrate malabsorption: D-xylose absorption test (xylose is normally absorbed by the intestine into the blood and excreted in the urine). In Tropical sprue less xylose is excreted in the urine.

– Imaging Techniques:

• Endoscopy to check for Villous atrophy

• Barium swallow to check for intestinal wall thickening.

• Jejunum biopsy to directly check for inflammation.

Treatment:

– Antibiotics to reduce bacterial overgrowth

– Nutritional replacement: folate and Vit-B12

– Sometime treatment may last for a 1 year. 

– Systemic disease caused by Tropheryma Whippelii infection, commonly affecting the lamine propria of the small bowel.

– Characterized by macrophages loaded

 with Tropheryma Whippelii

– In Whipple disease increase amount of macrophages in lamina propria compress the lacteals → chylomicrons cannot be transferred to lacteals from enterocytes → fat malabsorption and steatorhea.  

– Other locations affected by Whipple disease: Synovium of joints (arthritis), cardiac valves, lymph node, and CNS.

– AR deficiency of apolipoprotein B-48 and B-100

– Clinical features: 

• Malabsorption due to defective chylomicron formation (requires B-48)

• Absent plasma VLDL and LDL (requires B-100)

– Malignant proliferation of neuroendocrine cell, it is low grade malignancy

– Tumor cells contains contains neurosecretory granules that are positive for chromogranin

– The commone primary sites of caricinoid tumor are small/large intestine, stomach, liver, pancrease, lungs and thymus. In GIT small bowel is the most common site. 

– Grows as submucosal poly-like nodule.

– Can secret hormones such as histamin, bradykinin and serotonin. Serotonin is most often secreted

• Serotonin is released into portal circulation and metabolized by liver monoamine oxidase into 5-HIAA

• 5-HIAA is excreted in the urine.

– Metastasis to liver→serotonin enter the systemic circulation→carcinoid syndrome and carcinoid heart disease.

– Is a group of symptoms that  occur as a result of carcinoid tumor

–Symptoms inlcude: bronchospasm, diarrhea and flushing of skin. 

– Symptoms can be triggered by alcohol or emotional stress: stimulates serotonin release from the tumor.

Carcinoid hear disease:

– Right-sided valvular fibrosis (increased collagen) →tricuspid regurgitation and pulmonary valve stenosis; 

• Left-sided valvular lesions are not seen because in lungs MAO metabolizes serotonin.

–

Diagnosis:

– CT scan

– Octreoscan: Radiolabeled somatostatin analogue, octreotide, binds to somatostatin receptors on the tumor cells

– Urinalysis: 5-HIAA is increased

– Blood test: Niacin deficiency

Treatment: stop hormone production by endocrine cells and be done in the following way

– Somatostatin analogue→inhibits the release of hormones by tumor cells

– Decrease emotional stress and alcohol: reduces hormone release

– Surgical resection and chemotherapy of carcinoid tumor

– Acute inflammation of the appendix: most common cause of acute abdomen (Severe abdominal pain) 

– Caused by obstruction of the appendix by lymphoid hyperplasia ( children) and fecalith (adults)

– Clinical features:

•Preumbilical pain, fever nausea and vomiting. Pain eventually localizes to right lower quadrant (MacBurney point): Pain results due to pushing on the viceral nerve fiber near the appendix. 

• Appendix can rupture → peritonitis that present with Guarding (abdominal muscle tense up to avoid pain) and rebound tenderness.

• Periappendiceal abscess is common complication.

– Chronic relapsing inflammation of the bowel

– Cause is unknown, but is assumed to be due to abnormal immune response to enteric flora

– Usually affects young women (teens to 30s) with recurrent bouts of bloody diarrhea and abdominal pain.

– Most prevalent in the west, predominantly in Caucasian and Eastern European Jews. 

– Two major type of inflammatory bowel disease: Crohn Disease and Ulcerative Colitis.

– inflammatory bowel disease characterized by transmural inflammation (full-thickness inflammation), and is thought to be immune-related disorder (immune system triggered by pathogens)

– Locaton: From mouth to anus, terminal illeum most common site and rectum least common.

– Symptoms: Right lower quadrant pain (illeum most common) with non-bloody diarrhea

– Inflammation: Lymphoid aggregates with Granulomas (40% of cases) 

– Gross appearance: Coblestone mucosa, creeping fat and strictures

– Compilcation: Malabsorption with nutritional deficiency, calcium oxalate Nephrolithiasis (oxalate normally is present in the gut and not much is absorbed, but in inflammation the oxalate absorption increases and enters the blood. In the blood it binds to calcium especially in the filtrate of the glomerulus→calcium oxalate Nephrolithiasis), fistula formation and carcinoma if colonic disease is present.

– Associations: Ankylosing spondylitis, sacroiliitis, migratory polyarthritis, erythema nodosum and uveitis

– Smoking: Increase the risk 

–

– Inflammatory bowel disease characterized by mucosal and submucosal ulceration. This is an autoimmune disease. 

– Location: Begins in rectum and can spread up to cecum with continous lesions. The rest of GI is not affected

– Symptoms: Left lower quadrant pain (rectum) with bloody diarrhea

– Inflammation: crypt abscesses with neutrophils

– Gross Appearance: Pseudopolyps and loss of haustra

– Complication: Toxic megacolon and risk for carcinoma

– Association: Primary sclerosing cholangitis and P-ANCA positive. 

– smoking: Protects against Ulcerative Colitis. 

– Treatment: 1) Anti-inflammatory medication such as Sulfasalazine and mesalamine 2) In severe cases Immunossuppresant drugs such as Corticosterioid, Azothioprine and Cyclosporine.

–

– Hirschsprung disease is also known as congenital (present since birth) aganglionic (ganglions are missing in some parts of the colon) megacolon (enlarged colon due to obstruction).

– Defective relaxation and peristalsis of rectum and distal sigmoid colon.

– Caused by failure of gangion cell (derived from Neural crest cell) to decend to descend into myenteric and meisner plexus: Normally Neural crest cells differentiate into many different types of cell and one of them is Neuroblast. During fetal development Neuroblast descends from mouth to the rectum. In Hirschsprung disease defects occurs as Neuroblast descends to the rectum. 

– Two genes responsible for development of nervous plexus is RET and EDNRB. RET is associated with Down Syndrome. That is why Hirshsrpung Diseases is also associated with Ddown Syndrome.   

Clinical features based on obstruction:

– Failure to pass meconium in newborns

– Empty rectal vault in digital rectal exam

– Massive dilatation (megacolon) of bowel proximal to obstruction with risk of rupture

Diagnosis: 

– Abdominal x-ray with radiocontrast

– Rectal suction biopsy that includes both mucosa and submucosa revealing the lack of nervous plexus.

Treatment:

– resection of the bowel missing the ganglion cells. 

– Outpouching of mucosa and submucsoa through muscularis propria (false diverticula involves mucosa and submucosa. True Diverticual involves all the layers of the colon)

– Associated with constipation, straining and low fiber diet. Commonly occurs in adults.

– Usually arises in weak spots of the colon where the vasa recta traverses the muscle layer. Sigmoid is the most common location.

Symptoms are usually assymptomatic but complication include:

– Rectal bleeding (hematochezia) 

– Diverticulitis (due to obstructing fecal matetrial): Appendicitis like pain in the left lower quadrant.

– Fistula: diverticulitis → rupture→attachement of colon to local strcuture. Common fistula is colovesicular fistula:air in stool and urine).

Treatment:

– Antibiotics, high fiber diets and in severe cases surgical removal of the affected part.

https://www.youtube.com/watch?v=TL9_WKuNfu0

– Acquired malformation of mucosa and submucosal capillary bed

– Usually arises in the cecuma and ascending colon due to high wall tension

– rupture→hematochezia.

– Autosommal dominant disorder→thin-walled blood vessel in mouth and GIT. 

– Rupture→bleeding